Bibliographic details of the publications referred to by author in this specification are collected alphabetically at the end of the description.
The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates.
There is considerable interest in the identification, isolation and generation of mammalian stem and progenitor cells. Reference to “stem cells” and “progenitor cells” is generally understood to encompass a wide variety of cell types including both totipotent cells which can generate any cell type (including germ cells) and pluripotent precursor cells which can give rise to any cell type of the body except germ cells. Multipotent stem cells are capable of generating a more limited range of mature cell lineages. Some precursor cell types are still more differentiated and correspond to precursors capable of generating cells of specific cell lineages. These abilities serve as the basis for all the cellular differentiation and specialisation necessary for complete organ and tissue development. Accordingly, stem cells are the foundation for every organ, tissue and cell in the body.
Most of the body's specialised cells cannot be replaced by natural processes if they are seriously damaged or diseased. Since stem cells can be used to generate healthy and functioning specialised cells, they provide a mechanism to replace diseased or dysfunctional cells. Even in the context of conditions which are currently only treatable by whole organ replacement, stem cells may provide an alternative treatment regime directed to replacing the defective cellular populations within an organ, rather than the whole organ itself.
In light of the potential of stem cells to differentiate to any cell or tissue type of interest, their value in terms of providing a source of cells for generating specific cellular and tissue populations for medical therapies is infinite. To date, replacement of specific cellular populations (such as blood and bone marrow) and tissues (such as organs or parts thereof) relies on the harvesting and use of donor cellular populations and organs. However, the number of people needing transplants far exceeds the number of organs available. Similarly, even the supply of renewable cellular populations by live donors (such as blood donation) is struggling to keep up with demand.
Totipotent stem cells are generally isolated from embryos which are a few days old and can be used to create stem cell lines. However, in addition to the technical complexities in isolating and maintaining such stem cells, there currently exist significant ethical barriers to using this technology on a large scale. Stem cells can also be obtained from the umbilical cord of newborn babies. Although harvesting of these cells does not present the same extent of ethical issues as sourcing embryonic stem cells, the ongoing culturing of umbilical cord stem cells has proved problematic in that these cells can generally only be cultured for a limited period of time. However, stem cells can also be found in small numbers in various tissues of the adult body. Although generally not exhibiting totipotent characteristics, these adult stem cells are nevertheless multipotent and can therefore provide a useful source of cells for generating specific classes of differentiated cells. Accordingly, adult stem cells offer a potentially valuable stem cell source in that these cells may be more conveniently accessed and provide the potential for generating syngeneic cell and tissue transplants for a patient by isolating and using the patient's own stem cells.
In terms of adult stem cells, these cells have been identified in a range of tissues. Although typically programmed to form different cell types of their own tissue, it is believed that some adult stem cells may exhibit broader potentiality, known as stem cell “plasticity”. Accordingly, adult stem cells provide a potentially valuable ongoing source of stem cells, particularly to the extent that they are harvested from more accessible sources such as bone marrow and blood.
Nevertheless, even to the extent that blood and bone marrow provide a convenient stem cell source, the stem cell populations of these tissues are still extremely low and techniques for isolating, maintaining and expanding these stem cell populations are not efficient. There is therefore an ongoing need to develop methods of harvesting and culturing adult stem cells such that they can provide a practical and ongoing source of cellular material for therapeutic use.
In work leading up to the present invention it has been determined that when introduced, via vasculature, into a receptacle containing an acellular tissue support matrix (such as demineralised bone) the blood-derived cells present in the circulating blood will migrate from the vasculature into the matrix of the receptacle proper where they can undergo proliferation and/or differentiation. Of particular significance is the fact that for as long as the circulation through the vascularised receptacle is maintained, in the context of an appropriate microenvironment, the viability, proliferation and/or differentiation of the blood-derived cell population can be maintained indefinitely. Accordingly, this development now provides a very valuable means of providing an ongoing source of both blood-derived cells and the differentiated cellular populations derived therefrom, such as bone marrow cellular populations. There is therefore provided a source of cells for ongoing clinical or research use which does not involve the generation of cell lines.